Cav3.2 T-type Ca2+ channels regulate neuronal excitability, contributing to pain signaling, and their function is enhanced by H2S, a gasotransmitter. Cav3.2 is also expressed in certain cancer cells, and may affect cancer patients' prognosis. We have been studying the role of Cav3.2 in human prostate cancer LNCaP cells, particularly during neuroendocrine (NE)-like differentiation, which might be involved in hormone therapy resistance of prostate cancer. Cav3.2 and cystathionine γ-lyase (CSE), an H2S-generating enzyme, are overexpressed in LNCaP cells during NE differentiation, accompanied by upregulation of Egr-1 and downregulation of REST, which contribute to transcriptional upregulation of Cav3.2. These events may participate in increased secretion of mitogenic factors essential for proliferation of surrounding cells. Further, increased extracellular glucose levels accelerate functional upregulation and overexpression of Cav3.2 probably through asparagine-linked glycosylation of Cav3.2. Our study thus suggests a crucial role of the H2S/Cav3.2 system in NE-like differentiated LNCaP cells, which is promoted by hyperglycemia, being consistent with the clinical evidence that diabetes is a risk factor for castration-resistance of prostate cancer.

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